It has now been discovered that activated lymphocyte cell adhesion molecule (ALCAM)—also known as CD166—is the ligand of the innate immune receptor ILT3 that is expressed by DC and monocytes. It has been further discovered that the specific binding of ILT3 to its ligand CD166 on the surface of CD166-expressing cancer cells, arrested cancer cell growth and initiated apoptosis. Therefore, certain embodiments relate to methods and compositions for treating CD166-expressing cancers by administering ILT3Fc, full-length ILT3 or any CD166 ligand-binding fragment thereof.